H7N9: a low pathogenic avian influenza A virus infecting humans

Abstract

Human infections by the newly reassorted avian influenza A (H7N9) virus were reported for the first time in early 2013, and the virus was confirmed to be a low pathogenic avian influenza virus in poultry. Because continuously reported cases have been increasing since the summer of 2013, this novel virus poses a potential threat to public health in China and is attracting broad attention worldwide. In this review, we summarize and discuss the characteristics of the H7N9 virus revealed by the recent timely studies from the perspectives of epidemiology, host preference, clinical manifestations, immunopathogenesis, drug resistance, vaccine development, and burden of disease. This knowledge about the novel avian-origin H7N9 virus will provide a useful reference for clinical interventions of human infections and help to rapidly pave the way to develop an efficient and safe vaccine.

Figure 1

Illustration of the transmission routes of the novel H7N9 virus. H7 and N9 subtypes of undefined avian influenza viruses were transmitted into the poultry population, where H9N2 influenza viruses were circulating, and resulted in the varied genotypes of H7N9 reassortant viruses. Later on, humans were infected through the contact with virus-carrying poultry.

Figure 2

The T-cell immunogenic variation of H7N9 as compared with 2009 pH1N1. The previously well-defined antigenic epitopes of influenza virus (colored squares) are distributed in all of the major proteins (gray stripes, 10 well-defined proteins as illustrated herein) of the virus. The peptides have different HLA-restrictions (yellow for HLA-A2, pink for HLA-A24, green for HLA-A1, and cyan for HLA alleles from A3 supertype), which may cover a large majority of the population. The peptides with mutated sites when compared between H7N9 and 2009 pH1N1 are marked with a bias line in the square.

Figure 3

The molecular basis of the drug resistance of N9. Structural analysis of the oselatmivir carboxylate and zanamivir binding models in Anhui N9 and Shanghai N9. (a) Comparison of the oseltamivir binding model in Shanghai N9 (cyan) and Anhui N9 (green). (b) Comparison of the zanamivir binding models in Shanghai N9 (cyan) and Anhui N9 (green). The inhibitors and the surrounding residues are shown in sticks with hydrogen bonds and salt bridges indicated by dotted lines. The structure of Shanghai N9 is also displayed in surface representation. The binding models of peramivir and laninamivir with Shanghai N9 and Anhui N9 are quite similar to zanamivir.